Article

Resveratrol: How Much Wine Do You Have to Drink to Stay Healthy?

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Abstract

Resveratrol is a naturally occurring stilbene endowed with multiple health-promoting effects. It is produced by certain plants including several dietary sources such as grapes, apples, raspberries, blueberries, plums, peanuts, and products derived therefrom (e.g., wine). Resveratrol can be isolated and purified from these biological sources or synthesized in a few steps with an overall high yield. This compound and its glucoside, the trans-polydatin piceid, have received worldwide attention for their beneficial effects on cardiovascular, inflammatory, neurodegenerative, metabolic, and age-related diseases. These health-promoting effects are particularly attractive given the prevalence of resveratrol-based nutraceuticals and the paradoxical epidemiologic observation that wine consumption is inversely correlated to the incidence of coronary heart disease. However, the notion of resveratrol as a "magic bullet" was recently challenged by clinical trials showing that this polyphenol does not have a substantial influence on health status and mortality risk. In the present review, we discuss the proposed therapeuticattributes and the mode of molecular actions of resveratrol. We also cover recent pharmacologic efforts to improve the poor bioavailability of resveratrol and influence the transition between body systems in humans. We conclude with some thoughts about future research directions that might be meaningful for resolving controversies surrounding resveratrol.

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... The composition of stilbenes in red wine is much more complex than in white wine. Until today, more than (15) Relating to dietary sources, grapes and red wine are among the major sources of stilbenes in human nutrition and especially in European countries (Guerrero et al., 2009;Weiskirchen and Weiskirchen, 2016). However, it should be noted that stilbenes are also present in minor quantities in other foodstuffs such as peanut, pistachio, almonds, berries, banana, pineapple, apple, peach, passion fruit or dark chocolate (Neveu et al., 2010;Weiskirchen and Weiskirchen, 2016). ...
... Until today, more than (15) Relating to dietary sources, grapes and red wine are among the major sources of stilbenes in human nutrition and especially in European countries (Guerrero et al., 2009;Weiskirchen and Weiskirchen, 2016). However, it should be noted that stilbenes are also present in minor quantities in other foodstuffs such as peanut, pistachio, almonds, berries, banana, pineapple, apple, peach, passion fruit or dark chocolate (Neveu et al., 2010;Weiskirchen and Weiskirchen, 2016). Focusing only on grapes berries and wines, it is noteworthy that stilbene amounts can be extremely variable (Adrian et al., 2000;Guerrero et al., 2016;Hasan and Bae, 2017;Roldán et al., 2003;Vitrac et al., 2005). ...
... Stilbenes have demonstrated to possess a great range of biological activities potentially beneficial for human health such as neuroprotective, antioxidant and antitumor effects (Guerrero et al., 2009;Vang et al., 2011;Weiskirchen and Weiskirchen, 2016). Among the more recent research lines, stilbenes are gaining considerable interest as potential anti-obesity agents. ...
Thesis
Les polyphénols appartiennent à la famille des métabolites secondaires présents dans les plantes et majoritairement dans les baies de raisin. Ils jouent un rôle important dans la protection de la plante contre les stress biotiques et abiotiques. Ils ont un impact sur la qualité organoleptique des certains aliments comme ceux provenant du raisin et sont connus majoritairement pour leurs rôles bénéfiques pour la santé humaine. Une étude globale sur la composition phénolique et les activités biologiques (antioxydante, anti-inflammatoire et anti-diabète) des extraits phénoliques des pépins et pellicules de trois cépages rouges Merlot, Tannat et Syrah à différents stades de maturité a été réalisé durant cette thèse. Les extraits de pépins contiennent une teneur plus élevée de composés phénoliques que les extraits de pellicules pour tous les stades de maturation. La composition phénolique diffère selon le stade de maturité et le tissu de la baie de raisin (pépin ou pellicule). L’activité antioxydante des extraits a été déterminée par des tests spectrophotométriques (DPPH, ABTS et FRAP) et des paramètres électrochimiques. L’activité anti-inflammatoire a été suivie par l’inhibition de la production des EROs et NO par les cellules RAW 264.7 stimulées. L’activité anti-diabétique a été déterminée par la mesure d’inhibition de l’enzyme α- glucosidase. Les activités biologiques sont positivement corrélées avec la teneur en flavanols et négativement corrélées avec la teneur en anthocyanes et stilbènes. Les activités biologiques les plus importantes ont été mesurées avant la maturité pour tous les tests et dans les trois cépages étudiés.
... Resveratrol belongs to the smallest group of phenolic antioxidants, i.e., stilbenes, and is the most well-known and studied for its role in preventing cancer and neurodegenerative and cardiovascular diseases [2,[119][120][121]. Resveratrol exists in two isomeric forms as cisresveratrol and trans-resveratrol. ...
... Resveratrol (3,5,4 -trihydroxy-trans-stilbene, RES, chemical structure in Figure 11) is composed of two phenolic rings linked by an ethylene bridge. This is a natural polyphenol present in vegetables and fruits, especially in grapes skin and seeds, and in discrete amounts in red wines (see French paradox [119]). ...
... Resveratrol (3,5,4′-trihydroxy-trans-stilbene, RES, chemical structure in Figure 11) is composed of two phenolic rings linked by an ethylene bridge. This is a natural polyphenol present in vegetables and fruits, especially in grapes skin and seeds, and in discrete amounts in red wines (see French paradox [119]). Concerning RES detection, we report three examples of electrochemical sensors including gold nanoparticles and MIPs in the sensing interface. ...
Article
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Antioxidants play a central role in the development and production of food, cosmetics, and pharmaceuticals, to reduce oxidative processes in the human body. Among them, phenolic antioxidants are considered even more efficient than other antioxidants. They are divided into natural and synthetic. The natural antioxidants are generally found in plants and their synthetic counterparts are generally added as preventing agents of lipid oxidation during the processing and storage of fats, oils, and lipid-containing foods: All of them can exhibit different effects on human health, which are not always beneficial. Because of their relevant bioactivity and importance in several sectors, such as agro-food, pharmaceutical, and cosmetic, it is crucial to have fast and reliable analysis Rmethods available. In this review, different examples of gold nanomaterial-based electrochemical (bio)sensors used for the rapid and selective detection of phenolic compounds are analyzed and discussed, evidencing the important role of gold nanomaterials, and including systems with or without specific recognition elements, such as biomolecules, enzymes, etc. Moreover, a selection of gold nanomaterials involved in the designing of this kind of (bio)sensor is reported and critically analyzed. Finally, advantages, limitations, and potentialities for practical applications of gold nanomaterial-based electrochemical (bio)sensors for detecting phenolic antioxidants are discussed.
... Curcumin also exert similar effect but appears less effective than resveratrol. 5 Resveratrol is found in red wine, grapes, apple, peanut, soy, berries 64 . It has extremely low bioavailability, 64 and is impossible to eat enough to reach therapeutic concentration. ...
... 5 Resveratrol is found in red wine, grapes, apple, peanut, soy, berries 64 . It has extremely low bioavailability, 64 and is impossible to eat enough to reach therapeutic concentration. 65 However, resveratrol and its derivatives being different in potency, and hydrophobic nature of resveratrol, allows normal doses for longer durations to elicit benefits. ...
... 65 2) Single serving of red wine. 64 3) Apple, peanuts, soy or others in amount as desired. Drug interaction should be cautioned for resveratrol. ...
Article
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HEALTH can alternatively be also said as most synergistic aging to chronological age. Thus, figuring out approaches that lay path to reducing age, or simply anti-aging approach, help in this synergy, may even bypass this age constraint to some extent. In year 2009, a large scale European cohort study “MARK AGE STUDY” was designed to understand the aging changes aimed at reducing aging process or if possible stop it. Although there were many finding in the study, one in particular the oxidative changes associated to aging process, showed lower lycopene and MDA levels; and higher cysteine, α-tocopherol and 3- nitrotyrosine levels in long living individuals1 . However, following failure to find any dietary indication or supplementation, in relation to this study, it was sought possible to come with a dietary indication that would benefit in reducing the aging process. In year 2020, COVID 19 has emerged as a pandemic, which shows age related severity. So certain principles are created, and first applied in COVID 19 context, and evidences in favour of it were examined. A dietary instruction has been formulated labelled as Universal Dietary Adjunct Therapy, and is recommended to be included in normal dietary habits for a longer life-span, and as prophylaxis for chronic diseases and as adjunctive therapy to terminal illness and no-cure scenarios. Keywords: covid19, mark-age project, health, anti-aging diet, diet, universal adjunctive diet therapy, UDAT
... The recommended amount corresponds to a dose of 12.5 mg/kg body weight, in an adult weighing 80 kg. These concentrations are justified by animal experiments, most of which require a daily dose of 5 to 100 mg resveratrol/kg body weight to achieve a specific biological effect (Weiskirchen, 2016). ...
... Studies in humans have shown that resveratrol is a safe drug and is reasonably well tolerated at doses up to 5 g/day. Most of these therapeutic activities have only been determined in cell culture or preclinical models (Weiskirchen, 2016). ...
... However, these recommended daily doses are so high that it is not possible to absorb them by drinking wine or from other dietary sources. There is a need for more in-depth research to determine more accurate recommended doses of resveratrol for humans and, consequently, the amounts recommended for the treatment of specific diseases (Weiskirchen, 2016). ...
Article
Full-text available
Resveratrol is one of the phenolic compounds with high antioxidant activity. It occurs in nature in two forms, cis- and trans-. The cis- form occurs in grapes, but after being processed into wine, the trans- form is now present. The presence of resveratrol has been demonstrated in more than 72 plant species, mainly in the skins and on the surface of these plants. The physiological function is not completely known, but the highest values of resveratrol have been found in plants infected with microorganisms. Resveratrol is also a phytoalexin, a plant antibiotic that has a protective function in plants. A positive effect of resveratrol has also been observed in humans. According to research, the recommended daily dose should be 12.5 mg/kg body weight, which, according to the levels of resveratrol found in food, cannot be achieved with wine or any other food. Due to very poor bioavailability, where almost three quarters of resveratrol are metabolized in the body, consumption of the recommended daily dose is highly unrealistic. Despite its very low bioavailability, resveratrol has been shown to be an important cardioprotectant, has antitumor activity, is effective in the fight against aging and diabetes, and also acts as a neuroprotective agent. The main method for determining the resveratrol content in food is by high performance liquid chromatography. The aim of the review was to make an overview about chemical properties of resveratrol found in wine.
... Resveratrol belongs to the smallest group of phenolic antioxidants, i.e., stilbenes, and is the most well-known and studied for its role in preventing cancer and neurodegenerative and cardiovascular diseases [2,[119][120][121]. Resveratrol exists in two isomeric forms as cisresveratrol and trans-resveratrol. ...
... Resveratrol (3,5,4 -trihydroxy-trans-stilbene, RES, chemical structure in Figure 11) is composed of two phenolic rings linked by an ethylene bridge. This is a natural polyphenol present in vegetables and fruits, especially in grapes skin and seeds, and in discrete amounts in red wines (see French paradox [119]). ...
... Resveratrol (3,5,4′-trihydroxy-trans-stilbene, RES, chemical structure in Figure 11) is composed of two phenolic rings linked by an ethylene bridge. This is a natural polyphenol present in vegetables and fruits, especially in grapes skin and seeds, and in discrete amounts in red wines (see French paradox [119]). Concerning RES detection, we report three examples of electrochemical sensors including gold nanoparticles and MIPs in the sensing interface. ...
Article
Full-text available
Antioxidants play a central role in the development and production of food, cosmetics, and pharmaceuticals, to reduce oxidative processes in the human body. Among them, phenolic antioxidants are considered even more efficient than other antioxidants. They are divided into natural and synthetic. The natural antioxidants are generally found in plants and their synthetic counterparts are generally added as preventing agents of lipid oxidation during the processing and storage of fats, oils, and lipid-containing foods: All of them can exhibit different effects on human health, which are not always beneficial. Because of their relevant bioactivity and importance in several sectors, such as agro-food, pharmaceutical, and cosmetic, it is crucial to have fast and reliable analysis Rmethods available. In this review, different examples of gold nanomaterial-based electrochemical (bio)sensors used for the rapid and selective detection of phenolic compounds are analyzed and discussed, evidencing the important role of gold nanomaterials, and including systems with or without specific recognition elements, such as biomolecules, enzymes, etc. Moreover, a selection of gold nanomaterials involved in the designing of this kind of (bio)sensor is reported and critically analyzed. Finally, advantages, limitations, and potentialities for practical applications of gold nanomaterial- based electrochemical (bio)sensors for detecting phenolic antioxidants are discussed.
... Since its first certification, resveratrol has been identified in various plants such as plums, pistachios, berries, and peanuts. However, the most abundant source is represented by fresh grape skin, where it occurs in concentrations as high as 50-100 mg/g [109,110]. In recent years, due to its beneficial effects on health, resveratrol has received the attention of researchers [111]. ...
... In recent years, due to its beneficial effects on health, resveratrol has received the attention of researchers [111]. It is found in two isomeric forms, cis and trans, but the predominant isomer is trans, which has the most potent therapeutic effects due to its conformation [110,112]. In addition, it is also obtained via chemical or biotechnological synthesis from yeast Saccharomyces cerevisiae for industrial applications [113]. ...
Article
Full-text available
Liposome-based delivery systems have been studied and used more frequently in recent years due to their advantages, such as low toxicity, specificity, and the ability to protect the encapsulated substance from environmental factors, which could otherwise degrade the active compound and reduce its effectiveness. Given these benefits, many researchers have encapsulated polyphenols in liposomes, thus increasing their bioavailability and stability. Similarly, polyphenols encapsulated in liposomes are known to produce more substantial effects on targeted cells than unencapsulated polyphenols, while having minimal cytotoxicity in healthy cells. Although polyphenols play a role in preventing many types of disease and generally have beneficial effects on health, we solely focused on their chemopreventive effects on cancer through liposomes in this review. Our goal was to summarize the applicability and efficacy of liposomes encapsulated with different classes of polyphenols on several types of cancer, thus opening the opportunity for future studies based on these drug delivery systems.
... Therefore, both RSV and PD are used as anti-oxidants, and complement each other in clinical treatment. Various studies have confirmed that RSV and PD are widely used to treat several chronic diseases, such as atherosclerosis, pulmonary fibrosis, diabetes, cerebral ischemia, steatohepatitis, and various carcinomas ( Figure 1) [3,[5][6][7][8][9][10][11]. According to the biopharmaceutics classification system (BCS), RSV and PD are classified as category II due to their low solubility and high intestinal permeability [11][12][13]. ...
... RSV and PD have a wide range of pharmacological effects and are used clinically as complementary therapies [3,[5][6][7][8][9][10][11]. The main method of use is oral administration. ...
Article
Full-text available
Resveratrol (RSV) and polydatin (PD) have been widely used to treat several chronic diseases, such as atherosclerosis, pulmonary fibrosis, and diabetes, among several others. However, their low solubility hinders their further applications. In this work, we show that the solubility of PD can be boosted via its co-crystallization with L-proline (L-Pro). Two different phases of co-crystals, namely the RSV-L-Pro (RSV:L-Pro = 1:2) and PD-L-Pro (PD:L-Pro = 1: 3), have been prepared and characterized. As compared to the pristine RSV and PD, the solubility and dissolution rates of PD-L-Pro in water (pH 7.0) exhibited a 15.8% increase, whereas those of RSV-L-Pro exhibited a 13.8% decrease. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of pristine RSV, PD, RSV-L-Pro, and PD-L-Pro against lung cancer cell line A549 and human embryonic kidney cell line HEK-293 indicated that both compounds showed obvious cytotoxicity against A549, but significantly reduced cytotoxicity against HEK-293, with PD/PD-L-Pro further exhibiting better biological safety than that of RSV/RSV-L-Pro. This work demonstrated that the readily available and biocompatible L-Pro can be a promising adjuvant to optimize the physical and chemical properties of RSV and PD to improve their pharmacokinetics.
... Daily doses of RV are suggested for therapeutic intervention ranging from hundreds of milligrams to several grams based on animal studies. If a person tries to consume 1 g of RV per day, the consumed amount of food and drink should be depicted [50]. CFB is inhibited [63,64]. ...
... Very recent reports confirm that RV supplementation modulated JNK signaling, oxidative stress, and activity of caspase 3, thereby counteracting the severity of reproductive organs, Fig. 16. The promising beneficial effects of RV on different organs [50]. Asthma is the inflammatory condition of the respiratory tract, remodeling, and airway tremor is well known chronic disease around the globe. ...
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Resveratrol (RV) is a well-known polyphenolic compound in various plants, including grape, peanut, and berry fruits, which is quite famous for its association with several health benefits such as anti-obesity, cardioprotective neuroprotective, antitumor, antidiabetic, antioxidants, anti-age effects, and glucose metabolism. Significantly, promising therapeutic properties have been reported in various cancer, neurodegeneration, and atherosclerosis and are regulated by several synergistic pathways that control oxidative stress, cell death, and inflammation. Similarly, RV possesses a strong anti-adipogenic effect by inhibiting fat accumulation processes and activating oxidative and lipolytic pathways, exhibiting their cardioprotective effects by inhibiting platelet aggregation. The RV also shows significant antibacterial effects against various food-borne pathogens (Listeria, Campylobacter, Staphylococcus aureus, and E. coli) by inhibiting an electron transport chain (ETC) and F0F1-ATPase, which decreases the production of cellular energy that leads to the spread of pathogens. After collecting and analyzing scientific literature, it may be concluded that RV is well tolerated and favorably affects cardiovascular, neurological, and diabetic disorders. As such, it is possible that RV can be considered the best nutritional additive and a complementary drug, especially a therapeutic candidate. Therefore, this review would increase knowledge about the blend of RV as well as inspire researchers around the world to consider RV as a pharmaceutical drug to combat future health crises against various inhumane diseases. In the future, this article will be aware of discoveries about the potential of this promising natural compound as the best nutraceuticals and therapeutic drugs in medicine.
... Resveratrol-derived natural products, belonging to the class of polyphenolic stilbenes, have increasingly attracted the attention of the scientific community because of their diverse biological activities and intriguing molecular architectures [1][2][3]. Nonetheless, the growing interest in the pharmacological potential of this class of molecules derives from the poor understanding of the in vivo mechanisms of action of their parent compound resveratrol, which severely limits its therapeutic use [4] and the necessity to increase its low bioavailability and in vivo stability. Over the last years, several efforts were made towards the synthesis of complex natural resveratrol oligomers, by biomimetic and de novo approaches [1,[5][6][7][8][9]. ...
... The final Sonogashira coupling was performed with Pd(PPh 3 ) 4 and CuI in triethylamine at reflux for 8 h. The crude compound obtained was directly deprotected with KF to give the desired alkyne 32 in 38% yield, over two steps. ...
Article
Full-text available
The natural stilbenoid dehydro-δ-viniferin, containing a benzofuran core, has been recently identified as a promising antimicrobial agent. To define the structural elements relevant to its activity, we modified the styryl moiety, appended at C5 of the benzofuran ring. In this paper, we report the construction of stilbenoid-derived 2,3-diaryl-5-substituted benzofurans, which allowed us to prepare a focused collection of dehydro-δ-viniferin analogues. The antimicrobial activity of the synthesized compounds was evaluated against S. aureus ATCC29213. The simplified analogue 5,5′-(2-(4-hydroxyphenyl)benzofuran-3,5-diyl)bis(benzene-1,3-diol), obtained in three steps from 4-bromo-2-iodophenol (63% overall yield), emerged as a promising candidate for further investigation (MIC = 4 µg/mL).
... However, further research is needed to find out whether these effects observed in animal studies could be achieved in human cells as well. In addition, some doubts exist on the therapeutic activity of resveratrol because the research in older people showed no relationship between the urinary resveratrol metabolite concentration and inflammatory markers, cardiovascular disease, cancer, or mortality (Weiskirchen and Weiskirchen, 2016). ...
... When administered orally, resveratrol is rapidly metabolized and its bioavailability is quite low (Pannu and Bhatnagar, 2019). For this reason, it is not possible to reach the required doses to produce a therapeutic effect by drinking wine or consuming other foods (Weiskirchen and Weiskirchen, 2016). Therefore, a resveratrol-enriched wine may be more effective in terms of this compound intake. ...
Article
Full-text available
Resveratrol is a polyphenol with antioxidant properties and possible beneficial effects on human health. Grapes, peanuts, berries, cacao beans and red wine contain resveratrol. Resveratrol attracts attention due to its bioactive properties, however, the concentration of this compound is not high in grape and wine. Therefore, different studies have been carried out to increase resveratrol level in these products. Several factors such as the grapevine variety, the climatic conditions and the viticultural practices used to create stress on the vine affect the level of resveratrol. Winemaking technologies applied during pre-fermentation, fermentation and post–fermentation stages could also have an effect on the concentration of this stilbene. In addition, recent studies have evaluated biotechnological approaches through the use of different bacteria and yeast strains to produce wine with increased resveratrol content. In this review, the most important factors contributing to increase the resveratrol concentration in grapes and wines are examined. Besides, analytical methods to determine resveratrol content in wine are addressed.
... However, its main source is the skin of dark grapes (50-100 μg/g) [31,32]. Resveratrol is a phytoalexin, a compound produced by plants in response to the attack of pathogens and as a result of UV radiation and the action of heavy metals [33,34]. For this reason this compound exhibits several diverse biological activities ( Figure 3) [35]. ...
... Resveratrol is a phytoalexin, a compound produced by plants in response to the attack of pathogens and as a result of UV radiation and the action of heavy metals [33,34]. For this reason this compound exhibits several diverse biological activities ( Figure 3) [35]. ...
Article
Full-text available
Cancer diseases are currently one of the greatest health challenges in clinical medicine worldwide. Classic methods of treatment often lead to numerous side effects, including the development of multidrug resistance. For this reason, increasing hope is being placed on compounds of natural origin, mainly due to their pleiotropic effect on different types of cells, protective effect on normal cells and toxic effect on cancerous ones. The most studied group are the polyphenolic compounds, which include resveratrol. The effectiveness of polyphenols in the treatment and prevention of many diseases, including cancer of various origins, has become the basis of many scientific studies. The anticancer effect of resveratrol has been demonstrated at all stages of the carcinogenesis process. Additionally, whether administered by itself or in combination with cytostatics, it may play a significant role in the process of reversing multidrug resistance. A review of the effects of resveratrol in in vitro conditions proves that it has a stronger or weaker antiproliferative and proapoptotic effect on the cells of certain neoplasms of the gastrointestinal tract. Despite the differences in the effect of this compound on different types of cancer, a similar tendency can be observed especially regarding the correlation between the concentration of the compound and the incubation time on the one hand and the antitumour effect on the other hand. The information included in this review may prove helpful in planning in vivo and clinical studies in the future.
... This socalled 'French paradox' has been attributed to a moderate consumption of red wine, in which resveratrol (trans-3,5,4'-trihydroxystilbene), a natural polyphenol, has been found in significant amounts. Resveratrol was first isolated in 1939 from Veratrum grandiflorum's roots and is henceforth widely known as a phenolic compound with powerful antioxidant activity [271]. Resveratrol is present in several plants, including grape skins, grape seeds, giant knotweed, cassia seeds, passion fruit, white tea, plums and peanuts [272,273]. ...
... This so-called 'French paradox' has been attributed to a moderate consumption of red wine, in which resveratrol (trans-3,5,4'-trihydroxystilbene), a natural polyphenol, has been found in significant amounts. Resveratrol was first isolated in 1939 from Veratrum grandiflorum's roots and is henceforth widely known as a phenolic compound with powerful antioxidant activity [271]. Resveratrol is present in several plants, including grape skins, grape seeds, giant knotweed, cassia seeds, passion fruit, white tea, plums and peanuts [272,273]. ...
Article
Full-text available
Metabolic syndrome (MetS) is a cluster of several disorders, such as hypertension, central obesity, dyslipidemia, hyperglycemia, insulin resistance and non-alcoholic fatty liver disease. Despite health policies based on the promotion of physical exercise, the reduction of calorie intake and the consumption of healthy food, there is still a global rise in the incidence and prevalence of MetS in the world. This phenomenon can partly be explained by the fact that adverse events in the perinatal period can increase the susceptibility to develop cardiometabolic diseases in adulthood. Individuals born after intrauterine growth restriction (IUGR) are particularly at risk of developing cardiovascular diseases (CVD) and metabolic disorders later in life. It has been shown that alterations in the structural and functional integrity of the endothelium can lead to the development of cardiometabolic diseases. The endothelial progenitor cells (EPCs) are circulating components of the endothelium playing a major role in vascular homeostasis. An association has been found between the maintenance of endothelial structure and function by EPCs and their ability to differentiate and repair damaged endothelial tissue. In this narrative review, we explore the alterations of EPCs observed in individuals with cardiometabolic disorders, describe some mechanisms related to such dysfunction and propose some therapeutical approaches to reverse the EPCs dysfunction.
... Firstly, regarding dose, one should distinguish between doses compatible with human diet and supra dietary or pharmacological doses. A well-known dietary phytochemical, resveratrol, mainly present in wine, was the topic of a review entitled "How Much Wine Do You Have to Drink to Stay Healthy?" (4), opening the discussion of whether some health effects using supplements could be achieved following a balanced diet. In fact, a former editor of The Lancet wrote a letter entitled "Chateau Resveratrol," where he emphasized that the potential health benefits of wine, if any, came from ethanol and not from the small amounts of resveratrol (CAS 501-36-0) present in wine (5). ...
Article
The consumption of dietary phytochemicals has been associated with several health benefits and relevant biological activities. It is postulated that biotransformations of these compounds regulated by the microbiota, Phase I/II reactions, transport proteins, and deconjugating enzymes contribute not only to their metabolic clearance but also, in some cases, to their bioactivation. A number of factors (age, genetics, sex, physiopathological conditions, and the interplay with other dietary phytochemicals) modulating metabolic activities are important sources and contributors to the interindividual variability observed in clinical studies evaluating the biological activities of phytochemicals. In this review, we discuss all the processes that can affect the bioaccessibility and beneficial effects of these bioactive compounds. Herein, we argue that the role of these factors must be further studied to correctly understand and predict the effects observed following the intake of phytochemicals. This is, in particular, with regard to in vitro investigations, which have shown great inconsistency with preclinical and clinical studies. The complexity of in vivo metabolic activity and biotransformation should therefore be considered in the interpretation of results in vitro and their translation to human physiopathology.
... Resveratrol (RES) is an antioxidant naturally produced by plants in order to resist the invasion of pathogens, and is the main substance produced by phytotoxin reaction [4]. RES is a low molecular weight styrenic polyphenol compound with high content in grapes, mainly accumulated in grape leaves and peels to resist different mold infections, ultraviolet radiation and chemical damage [5,6]. RES can freely enter the lipid environment, which is a natural antioxidant and antibacterial agent [7]. ...
Article
Full-text available
Resveratrol with a high content in grapes has beneficial effects on inflammation, endothelial function, oxidative stress and cardiovascular and cerebrovascular diseases. Here, we propose a sensitive analytical method basing on the ultrasonic-assisted extraction followed by ultra-high performance liquid mass spectrometry to simultaneously determine trans-resveratrol (RES), trans-resveratrol 3-O-β-D-glucuronide, trans-resveratrol 4ʹ-O-β-D-glucuronide (R4G) in grapes. Single factor experiment and response surface methodology were used to optimize the pretreatment process of grape samples. The optimal conditions were as follows: extraction solvent-ethyl acetate, ultrasonic temperature 62 °C, ultrasonic time 20 min, ultrasonic power 90% and the volume of the extracted solvent 3500 μL. The method showed the good linearity (r ≥ 0.9917), the satisfactory intra-day (%RSD ≤ 11.3%) and inter-day precision (%RSD ≤ 14.5%) and low limit of quantification (0.1 μg/mL). This proposed method was successfully applied to determine RES, R3G, R4G in different grapes, achieving satisfactory recoveries (88.8–116.9%). Thus, this method established in this study is simple and time-saving, which will be helpful to the development and utilization of RES, R3G, R4G in grapes in food and pharmaceutical industries.
... A recent study of people aged from 71 to 81 years, had reported that the consumption of foods rich in biologically active compounds and especially anthocyanins has improved memory. [15] Also bioavailability and absorption of anthocyanins are influenced by: release from food matrices and sol-ubility in gastrointestinal secretions also interaction with gastrointestinal components, chemical degra-dation or metabolism and epithelial cell permeability [2,8,29]. ...
Conference Paper
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Представлен материал о перспективе применения традиционных (национальных) сортов и высокопродуктивных гибридов томатов стран Евразийского экономического сообщества для создания концентрированных форм функциональных ингредиентов, богатых биологически активными веществами. Показана возможность производства пробиотических препаратов на основе культур комменсальных микроорганизмов штаммов, способных продуцировать бактериоцины. The article presents material on the prospect of using traditional (national) varieties and highly productive tomato hybrids from the countries of the Eurasian economic community to create concentrated forms of functional ingredients rich in biologically active substances. The possibility of producing probiotic preparations based on cultures of commensal microorganisms of strains capable of producing bacteriocins has been shown.
... Stilbenes possess different biological and pharmacological activities which potentially beneficial for human health such as neuroprotective, antitumor, and antioxidant effects. Berries such as blueberries and cranberries contain stilbenes [62,63]. ...
Article
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Functional plant-based foods (such as fruits, vegetables, and berries) can improve health, have a preventive effect, and diminish the risk of different chronic diseases during in vivo and in vitro studies. Berries contain many phytochemicals, fibers, vitamins, and minerals. The primary phytochemicals in berry fruits are phenolic compounds including flavonoids (anthocyanins, flavo-nols, flavones, flavanols, flavanones, and isoflavonoids), tannins, and phenolic acids. Since berries have a high concentration of polyphenols, it is possible to use them for treating various diseases pharmacologically by acting on oxidative stress and inflammation, which are often the leading causes of diabetes, neurological, cardiovascular diseases, and cancer. This review examines commonly consumed berries: blackberries, blackcurrants, blueberries, cranberries, raspberries, black raspberries, and strawberries and their polyphenols as potential medicinal foods (due to the presence of pharmacologically active compounds) in the treatment of diabetes, cardiovascular problems, and other diseases. Moreover, much attention is paid to the bioavailability of active berry components. Hence, this comprehensive review shows that berries and their bioactive compounds possess medicinal properties and have therapeutic potential. Nevertheless, future clinical trials are required to study and improve the bioavailability of berries' phenolic compounds and extend the evidence that the active compounds of berries can be used as medicinal foods against various diseases.
... Resveratrol (3, 5, 4′-trihydroxystilbene) is a natural polyphenol produced by plants including grapes and berries and widely used as a food supplement (34,35). It interacts with and modulates the activity of at least 20 mammalian proteins including CRAC channels and VGCCs (36). ...
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Tuberculosis (TB) remains a challenging global health concern and claims more than a million lives every year. We lack an effective vaccine and understanding of what constitutes protective immunity against TB to inform rational vaccine design. Moreover, treatment of TB requires prolonged use of multi-drug regimens and is complicated by problems of compliance and drug resistance. While most Mycobacterium tuberculosis (Mtb) bacilli are quickly killed by the drugs, the prolonged course of treatment is required to clear persistent drug-tolerant subpopulations. Mtb’s differential sensitivity to drugs is, at least in part, determined by the interaction between the bacilli and different host macrophage populations. Therefore, to design better treatment regimens for TB, we need to understand and modulate the heterogeneity and divergent responses that Mtb bacilli exhibit within macrophages. However, developing drugs de-novo is a long and expensive process. An alternative approach to expedite the development of new TB treatments is to repurpose existing drugs that were developed for other therapeutic purposes if they also possess anti-tuberculosis activity. There is growing interest in the use of immune modulators to supplement current anti-TB drugs by enhancing the host’s antimycobacterial responses. Ion channel blocking agents are among the most promising of the host-directed therapeutics. Some ion channel blockers also interfere with the activity of mycobacterial efflux pumps. In this review, we discuss some of the ion channel blockers that have shown promise as potential anti-TB agents.
... It is a natural phytoalexin that exists mainly in the trans structure. It has been detected in >70 plants, including eucalyptus and banyan, and dietary sources mainly include red grapes, mulberries and red wine, with the highest content found in the Chinese traditional medicine, Polydatin (2,3). Metformin (MET) is a first-line anti-diabetic drug that is widely used in the treatment of T2DM. ...
Article
Resveratrol (RSV) and metformin (MET) play a role in the treatment of diabetes; however, the mechanisms through which they mediate insulin resistance by regulating long non‑coding RNAs (lncRNAs) remain unknown. The present study was conducted to determine whether RSV and MET can improve insulin resistance in the livers of high‑fat diet (HFD)‑fed mice by regulating lncRNAs. C57BL/6J mice were fed a HFD for 8 weeks to establish a model of insulin resistance. The mice were subsequently treated with RSV or MET for 8 weeks and liver tissue samples were then collected. High‑throughput sequencing was utilized to analyze mouse liver tissue samples to obtain differential lncRNA expression profiles. RSV or MET both reduced the blood glucose levels, the insulin index and the area under the curve in HFD‑fed mice. Treatment also improved liver structure and decreased lipid deposition in liver tissues, as shown by H&E and Oil Red O staining. Compared with the MET group, there were 55 lncRNAs and 19 mRNAs with a differential expression. In total, eight lncRNAs were randomly selected and evaluated by reverse transcription‑quantitative PCR (RT‑qPCR). The results of seven lncRNAs corresponded to those of the sequencing analysis. Pathway analysis revealed that the PI3K/Akt signaling pathway had the highest enrichment score. In addition, the results of western blot analysis and RT‑qPCR revealed that the expression levels of forkhead box O1, glucose‑6‑phosphatase catalytic subunit 1 and phosphoenolpyruvate carboxykinase 1 in the RSV and MET groups were significantly decreased compared with those in the HFD group. NONMMUT034936.2 and G6PC target genes exhibited similar expression patterns, indicating that RSV and MET may affect the PI3K/Akt signaling pathway through NONMMUT034936.2 to attenuate insulin resistance. On the whole, the present study provides novel biomarkers or contemporary perspectives for the use of RSV and MET in the treatment of insulin resistance and diabetes.
... Sugars represent the main groups of metabolites in wines, while organic acids, amino acids, and phenolic compounds represent other minor metabolites, which together constitute the basic nutritional quality of wines fermented with yeast strains [143]. Grapes and red wines are the major dietary sources of stilbenes, which influence human health through antioxidant, anti-obesity, anti-tumor, and neuroprotective effects, with resveratrol as a typical representative compound [144,145]. HPLC-MS is the most commonly applied technique for determining phenolic compounds, particularly stilbenes [146]. Tabago et al. [49] successfully summarized the potential of NMR metabolomics in terms of geographical origin, variety, vintage, fermentation, and quality evaluation of wine and alcohol, to distinguish wines under different fermentation conditions such as bacterial and yeast strains and agricultural cultivars [147]. ...
Article
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Fermentation is an important process that can provide new flavors and nutritional and functional foods, to deal with changing consumer preferences. Fermented foods have complex chemical components that can modulate unique qualitative properties. Consequently, monitoring the small molecular metabolites in fermented food is critical to clarify its qualitative properties and help deliver personalized nutrition. In recent years, the application of metabolomics to nutrition research of fermented foods has expanded. In this review, we examine the application of metabolomics technologies in food, with a primary focus on the different analytical approaches suitable for food metabolomics and discuss the advantages and disadvantages of these approaches. In addition, we summarize emerging studies applying metabolomics in the comprehensive analysis of the flavor, nutrition, function, and safety of fermented foods, as well as emphasize the applicability of metabolomics in characterizing the qualitative properties of fermented foods.
... The antioxidant effects of resveratrol have been thought to play a role in the "French Paradox," with consumption of red wine in moderation among the French assumed to be partially responsible for low rates of cardiovascular disease, despite high rates of smoking and saturated fat consumption. 64 Scientific study went on to demonstrate that resveratrol supplementation reduces oxidative stress and enhances expression of antioxidative genes, while also improving vascular function. [65][66][67] Resveratrol is also thought to exert anti-inflammatory effects through COX-2 inhibition. ...
Article
Botanical medicines may prevent or hamper colon carcinogenesis through a variety of mechanisms, such as induction of apoptosis or cell cycle regulation. As evidenced by primary and secondary prevention studies using aspirin, inflammation and COX-2 expression are important drivers of colon carcinogenesis, promoting both the initiation and progression of colon cancer. Some botanical medicines may exert a protective effect by quelling such inflammation. This article reviews pertinent clinical or preclinical evidence for the preventive effects of garlic, curcumin, berberine, Boswellia, ginseng, ginger, resveratrol, and rosmarinic acid, in reference to colorectal cancer. While the data for medicinal plants and their constituents remain largely preclinical, there are several areas of interest that warrant additional study.
... These molecules are structurally linked since they all have the same stilbene backbone, but the substituent groups on the rings are different with regard to type and positions. Stilbene-based compounds have been intensively investigated in recent years due to their various biological effects on human beings [86,87]. 2,3 diphenyl cyclopropyl methyl phenyl sulphoxide is proven to act as a promising potential therapeutic agent against ovarian cancer stem cell lines [88,89]. ...
Article
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Severe acute respiratory syndrome coronavirus 2 was originally identified in Wuhan city of China in December 2019 and it spread rapidly throughout the globe, causing a threat to human life. Since targeted therapies are deficient, scientists all over the world have an opportunity to develop novel drug therapies to combat COVID-19. After the declaration of a global medical emergency, it was established that the Food and Drug Administration (FDA) could permit the use of emergency testing, treatments, and vaccines to decrease suffering, and loss of life, and restore the nation's health and security. The FDA has approved the use of remdesivir and its analogs as an antiviral medication, to treat COVID-19. The primary protease of SARS-CoV-2, which has the potential to regulate coronavirus proliferation, has been a viable target for the discovery of medicines against SARS-CoV-2. The present research deals with the in silico technique to screen phytocompounds from a traditional medicinal plant, Bauhinia variegata for potential inhibitors of the SARS-CoV-2 main protease. Dried leaves of the plant B. variegata were used to prepare aqueous and methanol extract and the constituents were analyzed using the GC-MS technique. A total of 57 compounds were retrieved from the aqueous and methanol extract analysis. Among these, three lead compounds (2,5 dimethyl 1-H Pyrrole, 2,3 diphenyl cyclopropyl methyl phenyl sulphoxide, and Benzonitrile m phenethyl) were shown to have the highest binding affinity (−5.719 to −5.580 kcal/mol) towards SARS-CoV-2 Mpro. The post MD simulation results also revealed the favorable confirmation and stability of the selected lead compounds with Mpro as per trajectory analysis. The Prime MM/GBSA binding free energy supports this finding, the top lead compound 2,3 diphenyl cyclopropyl methyl phenyl sulphoxide showed high binding free energy (−64.377 ± 5.24 kcal/mol) towards Mpro which reflects the binding stability of the molecule with Mpro. The binding free energy of the complexes was strongly influenced by His, Gln, and Glu residues. All of the molecules chosen are found to have strong pharmacokinetic characteristics and show drug-likeness properties. The lead compounds present acute toxicity (LD50) values ranging from 670 mg/kg to 2500 mg/kg; with toxicity classifications of 4 and 5 classes. Thus, these compounds could behave as probable lead candidates for treatment against SARS-CoV-2. However further in vitro and in vivo studies are required for the development of medication against SARS-CoV-2.
... A recent study of people aged from 71 to 81 years, had reported that the consumption of foods rich in biologically active compounds and especially anthocyanins has improved memory. [15] Also bioavailability and absorption of anthocyanins are influenced by: release from food matrices and sol-ubility in gastrointestinal secretions also interaction with gastrointestinal components, chemical degra-dation or metabolism and epithelial cell permeability [2,8,29]. ...
Conference Paper
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Zharkova, I.M.; Harutyunyan, N.A.; Pepoyan, A.Z.; Pochitskaya, I.M. Tomatoes: A modern view on processing and possibility of cooperation of the Eurasian Economic Union member countries. In Proceedings of the III International Congress “Science, Nutrition and Health”, Minsk, Belarus, 24–25 June 2021; Lovkis, Z.V., Ed.; Belarusian Science: Minsk, Belarus, 2021; Part 2; pp. 83–87 стр. 83-87 Представлен материал о перспективе применения традиционных (национальных) сортов и высокопродуктивных гибридов томатов стран Евразийского экономического сообщества для создания концентрированных форм функциональных ингредиентов, богатых биологически активными веществами. Показана возможность производства пробиотических препаратов на основе культур комменсальных микроорганизмов штаммов, способных продуцировать бактериоцины. The article presents material on the prospect of using traditional (national) varieties and highly productive tomato hybrids from the countries of the Eurasian economic community to create concentrated forms of functional ingredients rich in biologically active substances. The possibility of producing probiotic preparations based on cultures of commensal microorganisms of strains capable of producing bacteriocins has been shown.
... Among this broad class of compounds, resveratrol has gaining a key scientific interest due its good anticancer and antioxidant effects (Summerlin et al., 2015). Despite its isolation in 1939 firstly from the roots of the Japanese plant Polygonum cuspidatum (Timmers et al., 2012), resveratrol is an important antioxidant present abundantly in red grapes, red wine, and a variety of other dietary sources, such as peanuts, raspberries, blueberries, and mulberries (Chong et al., 2009;Jasiński et al., 2013;Weiskirchen and Weiskirchen, 2016;Jeandet et al., 2021). ...
... Many studies have also reported human health benefits resulting from the dietary consumption of stilbenes. tR has been largely studied for its antioxidant, antiinflammatory, immunomodulatory and anti-angiogenic effects, and for its potential roles in chemoprevention of cancer and cardiovascular diseases [6][7][8]. ...
Article
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Citation: Hurtado-Gaitán, E.; Sellés-Marchart, S.; Hartwell, J.; Martínez-Esteso, M.J.; Bru-Martínez, R. Abstract: In grapevine, trans-Resveratrol (tR) is produced as a defence mechanism against stress or infection. tR is also considered to be important for human health, which increases its interest to the scientific community. Transcriptomic analysis in grapevine cell cultures treated with the defence response elicitor methyl-β-cyclodextrin (CD) revealed that both copies of PHOSPHOENOLPYRU-VATE CARBOXYLASE KINASE (PPCK) were down-regulated significantly. A role for PPCK in the defence response pathway has not been proposed previously. We therefore analysed the control of PPCK transcript levels in grapevine cell cultures and leaves elicited with CD. Moreover, phospho-enolpyruvate carboxylase (PPC), stilbene synthase (STS), and the transcription factors MYB14 and WRKY24, which are involved in the activation of STS transcription, were also analysed by RT-qPCR. The results revealed that under CD elicitation conditions PPCK down-regulation, increased stilbene production and loss of PPC activity occurs in both tissues. Moreover, STS transcripts were co-induced with MYB14 and WRKY24 in cell cultures and leaves. These genes have not previously been reported to respond to CD in grape leaves. Our findings thus support the hypothesis that PPCK is involved in diverting metabolism towards stilbene biosynthesis, both for in vitro cell culture and whole leaves. We thus provide new evidence for PEP being redirected between primary and secondary metabolism to support tR production and the stress response.
... Whereas extensive literature indicates that both compounds exhibit a similar, beneficial effects upon health and longevity in prokaryotes and lower eukaryotes, their respective effects in higher eukaryotes, including rodents and humans, are less clear. However, both antioxidants may contribute in concert to numerous, but still controversial, findings of RSV actions in human beings [84], and may play a role in the well-known principles of the "Mediterranean way of drinking and longevity " [85]; both compounds coexist in red grapes and wines [15,[86][87][88], but their possible synergistic effects in various experimental models have not been studied. ...
Article
Aging-related impaired body structure and functions may be, at least partially, caused by elevated oxidative stress. Melatonin (MEL) and resveratrol (RSV) may act as antioxidant and anti-aging compounds, but these actions in experimental animals and humans are controversial. Herein, a rat model of aging was used to study the long-term sex-related effects of MEL and RSV treatment on body mass and blood/plasma parameters of DNA damage, oxidative status (glutathione and malondialdehyde levels), and concentrations of sex hormones. Starting from the age of 3mo, for the next 9mo or 21mo male and female Wistar rats (n = 4-7 per group) were given water to drink (controls) or 0.1% ethanol in water (vehicle), or MEL or RSV (each 10 mg/L vehicle). DNA damage in whole blood cells was tested by comet assay, whereas in plasma, glutathione, malondialdehyde, and sex hormones were determined by established methods. Using statistical analysis of data by ANOVA/Scheffe post hoc, we observed a similar sex- and aging-dependent rise of body mass in both sexes and drop of plasma testosterone in control and vehicle-treated male rats, whose pattern remained unaffected by MEL and RSV treatment. Compared with controls, all other parameters remained largely unchanged in aging and differently treated male and female rats. We concluded that the sex- and aging-related pattern of growth and various blood parameters in rats were not affected by the long-term treatment with MEL and RSV at the estimated daily doses (300-400 µg/kg b.m.) that exceed usual moderate consumption in humans.
... The use of yeasts with low adsorption capacity for phenolic compounds, such as anthocyanins (126) and resveratrol (147), should also be taken into account, due to their adsorption by the cell walls of yeasts, which due to their non-polar character, have shown greater adsorption capacity for acylated anthocyanins (from higher to lower adsorption: coumarilated > caffeinated > acetylated) compared to the nonacylated ones (148,149), indicating an inverse relationship between the polarity of anthocyanins and their adsorption. This would also explain the adsorption of resveratrol (with low hydrophilic character) (123,150), by the cell walls of yeasts. ...
Article
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There is ample evidence regarding the health benefits of red wine consumption due to its content of phenolic compounds, as an alternative to improve the state of health and prevent various diseases, being the implementation of procedures that allow a greater extraction and stability of phenolic compounds during the elaboration a key aspect. The first part of this review summarizes some studies, mostly at the preclinical level, on the mechanisms by which phenolic compounds act in the human organism, taking advantage of their antioxidant, anti-inflammatory, antitumor, antithrombotic, antiatherogenic, antimicrobial, antiviral, and other activities. Although the migration of grape components into the must/wine occurs during the winemaking process, the application of new technologies may contribute to increasing the content of phenolic compounds in the finished wine. Some of these technologies have been evaluated on an industrial scale, and in some cases, they have been included in the International Code of Oenological Practice by the International Organization of Vine and Wine (OIV). In this sense, the second part of this review deals with the use of these novel technologies that can increase, or at least maintain, the polyphenol content. For example, in the pre-fermentative stage, phenolic extraction can be increased by treating the berries or must with high pressures, pulsed electric fields (PEF), ultrasound (US), e-beam radiation or ozone. At fermentative level, yeasts with high production of pyranoanthocyanins and/or their precursor molecules, low polyphenol absorption, and low anthocyanin-β-glucosidase activity can be used. Whereas, at the post-fermentative level, aging-on-lees (AOL) can contribute to maintaining polyphenol levels, and therefore transmitting health benefits to the consumer.
... However, the dose of alcohol that causes leaky gut is still debated [73]. Given that red wine consumption is generally considered beneficial due to the reported benefits of resveratrol for healthy ageing [74], there might be a trade-off between the effects of alcohol and resveratrol in wine. Notably, the doses of resveratrol that promote healthy ageing have not been determined [75][76][77][78]. ...
Article
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NF-κB is generally recognized as an important regulator of ageing, through its roles in cellular senescence and inflammatory pathways. Activated in virtually all cell-cell communication networks of the immune system, NF-κB is thought to affect age-related defects of both innate and adaptive immune cells, relevant to inflamm-ageing and declining adaptive immunity, respectively. Moreover, the family of NF-κB proteins that exist as heterodimers and homodimers exert their function beyond the immune system. Given their involvement in diverse areas such as DNA damage to metabolism, NF-κB has the potential to serve as linkages between known hallmarks of ageing. However, the complexity of NF-κB dimer composition, dynamic signaling, and tissue-specific actions has received relatively little attention in ageing research. Here, we discuss some areas where further research may bear fruit in our understanding the impact of NF-κB in healthy ageing and longevity.
... However, several studies (including the current one) are being conducted to use these additive interactions as an advantage to decrease the dose of medication when used in combination with resveratrol [30,67]. Several human and animal studies focused on resveratrol's safety have been reported [35] and demonstrating that its overall low toxicity in humans encourages further translational research [71][72]. ...
Article
Background: Renovascular hypertension elicits cardiac damage and remodeling. Two-kidney, one-clip (2K1C) is an experimental model used to study hypertension pathophysiology. In this model, the renin-angiotensin-system (RAS) is overactive due to renal artery stenosis, leading to cardiac remodeling. Redox mechanisms underlying RAS activation mediate hypertension-induced cardiovascular damage. Preclinical studies and clinical trials demonstrated resveratrol's protective effects in cardiovascular diseases, mainly attributed to its antioxidant properties. We hypothesized resveratrol alone or in combination with an angiotensin-converting enzyme (ACE) inhibitor would be beneficial against cardiac damage caused by renovascular hypertension. Objective: We investigated the benefits of resveratrol against cardiac remodeling in 2K1C rats compared with captopril. Methods: Male Wistar rats underwent unilateral renal stenosis - 2K1C Goldblatt model of hypertension. Systolic Blood Pressure (SBP) was measured before and 6 weeks after surgery. Hypertensive 2K1C rats presented SBP≥160 mmHg. From the 6th week after the surgery, the animals received oral resveratrol (20 mg/kg), captopril (12 mg/kg), or their combination for 3 times per week for 3 weeks. Whole heart hypertrophy was evaluated. Histological assays assessed left ventricle hypertrophy and fibrosis. Results: Renovascular hypertension caused cardiac hypertrophy, accompanied by increased myocyte diameter and collagen deposition. Resveratrol reduced 2K1C rats' SBP and whole heart hypertrophy, independently of captopril. Resveratrol caused a higher reduction in ventricular hypertrophy than captopril. Collagen deposition was greater reduced by 2K1C treated only with resveratrol than with captopril alone or combined with resveratrol. Conclusion: Independent of captopril, resveratrol prompts cardioprotective effects on cardiomyocyte remodeling and fibrosis resulting from renovascular hypertension in 2K1C rats.
... al., 1997;Paixao et al., 2007). Important antioxidant compounds include caffeic acid, catechin, chlorogenic acid, epicatechin, ferulic acid, myricetin, protocatechuic acid, quercetin, and resveratrol (Weiskirchen and Weiskirchen, 2016). ...
... According to Scalbert and Williamson [126], the daily consumption of polyphenols is estimated at around 1 g with major consumption of flavonoids (60%) comprising 460 mg of proanthocyanidins, 200 mg of catechins, 180-215 mg of anthocyanins and 115 mg of flavones and flavonols [126,131]. Stilbenes are found in low quantities in the human diet, except for resveratrol, widely present in various quantities in dark chocolate (350 µg/kg), red grapes (92-1604 µg/kg fresh weight) and white grapes (59-1759 µg/kg fresh weight) [132]. Linseed is the richest dietary source of lignans containing secoisolariciresinol (up to 3.7 g/kg dry weight) and low quantities of matairesinol [133]. ...
Article
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Type 2 diabetes is a metabolic disease mainly associated with insulin resistance during obesity and constitutes a major public health problem worldwide. A strong link has been established between type 2 diabetes and periodontitis, an infectious dental disease characterized by chronic inflammation and destruction of the tooth-supporting tissue or periodontium. However, the molecular mechanisms linking periodontal bacteria and insulin resistance remain poorly elucidated. This study aims to summarize the mechanisms possibly involved based on in vivo and in vitro studies and targets them for innovative therapies. Indeed, during periodontitis, inflammatory lesions of the periodontal tissue may allow periodontal bacteria to disseminate into the bloodstream and reach tissues, including adipose tissue and skeletal muscles that store glucose in response to insulin. Locally, periodontal bacteria and their components, such as lipopolysaccharides and gingipains, may deregulate inflammatory pathways, altering the production of pro-inflammatory cytokines/chemokines. Moreover, periodontal bacteria may promote ROS overproduction via downregulation of the enzymatic antioxidant defense system, leading to oxidative stress. Crosstalk between players of inflammation and oxidative stress contributes to disruption of the insulin signaling pathway and promotes insulin resistance. In parallel, periodontal bacteria alter glucose and lipid metabolism in the liver and deregulate insulin production by pancreatic β-cells, contributing to hyperglycemia. Interestingly, therapeutic management of periodontitis reduces systemic inflammation markers and ameliorates insulin sensitivity in type 2 diabetic patients. Of note, plant polyphenols exert anti-inflammatory and antioxidant activities as well as insulin-sensitizing and anti-bacterial actions. Thus, polyphenol-based therapies are of high interest for helping to counteract the deleterious effects of periodontal bacteria and improve insulin resistance.
... Even though RES is found in a breadth of plant-based foods (e.g., red wine, berries, peanuts, and dark chocolate), the naturally occurring concentrations of RES are not substantial enough (e.g., 0.1-0.7 mg/L in red wine) to reasonably attain the therapeutic values reported in the scientific literature (e.g., an oral dose of approximately 10 mg/kg body) [86][87][88]. ...
Chapter
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Periodontitis is a globally prevalent inflammation-mediated disease that can result in varying degrees of destruction to the tissues supporting the teeth. The microbial pathogenic dysbiosis, oxidative stress, and deregulated inflammation, found in patients with periodontitis, make it a multifaceted condition that is difficult to fully resolve. Further to this, periodontitis has been associated with other systemic inflammatory conditions. Trans-resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a plant-derived molecule present in many foods, which have been shown to exhibit antimicrobial, antioxidant, anti-inflammatory, and regenerative properties. However, trans-resveratrol has been reported to have physicochemical shortcomings, which make its clinical translation a challenge. This review outlines a critical analysis of identified samples from the scientific literature that was conducted to assess the potential of RES as a viable therapeutic for periodontitis. The potential for the improvement of the limiting pharmacological profile of trans-resveratrol via nanoformulation is also explored.
... Resveratrol (RSV), a polyphenolic molecule, is found in grapes, wine, peanuts, and blueberries [23]. It has a wide range of biological activities, including anti-inflammatory [24] and antioxidant properties [25]. The antioxidant activity of RSV occurs by scavenging the free radicals and enhancing the activity of the antioxidant defense system to protect against oxidative injury [26]. ...
Article
Fenitrothion (FNT), a commonly used organophosphate, can cause oxidative damage and apoptosis on various organs. However, the underlying mechanisms for FNT-induced cardiotoxicity did not formally report. Here, we have evaluated the possible ameliorative roles of resveratrol (RSV) against FNT-induced cardiac apoptosis in male rats through the sirtuin1 (SIRT1)/c-Jun N-terminal kinase (c-JNK)/p53 pathway concerning pro-oxidant and inflammatory cytokines. Forty-eight male rats were equally grouped into control, RSV (20 mg/kg), 5-FNT (5 mg/kg), 10-FNT (10 mg/kg), 20-FNT (20 mg/kg), 5-FNT-RSV, 10-FNT-RSV, and 20-FNT-RSV where all doses administrated by gavage for four weeks. The present findings demonstrated that RSV markedly diminished the level of hyperlipidemia and elevation in lactate dehydrogenase (LDH), total creatine kinase (CK-T), and troponin T (TnT) levels following FNT intoxication. Furthermore, RSV significantly reduced FNT-induced cardiac oxidative injury by reducing malondialdehyde (MDA) level and improving the levels of glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and acetylcholinesterase (AchE). Also, the levels of interleukin-1β (IL1β,), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were significantly attenuated in the co-treated groups. Moreover, RSV alleviated the histopathological changes promoted by FNT and repaired the transcript levels of SIRT1, c-JNK, and caspase-9/3 along with p53 immunoreactivity. In silico study revealed that the free binding energies of RSV complexes with protein and DNA sequences of SIRT1 were lower than docked complexes of FNT. Therefore, RSV reserved myocardial injury-induced apoptosis following exposure to FNT by modulating the SIRT1/c-JNK/p53 pathway through cellular redox status and inflammatory response improvements.
Chapter
Neurons are highly energy- and oxygen-consuming cells needed for vital and complex brain functions. Dysfunction in energy production and imbalance in reactive oxygen species are the consequence of impaired mitochondrial function, a crucial organelle for different cellular signaling pathways. Undeniably, mitochondrial dysfunction has been implicated in the pathogenesis of several neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Therefore, strategies focusing on the maintenance of mitochondrial function, with antioxidant and antiinflammatory drugs are of huge interest. Resveratrol (RV) is a polyphenolic compound with antioxidant, antiinflammatory, and antiapoptotic effects. Previous studies showed that RV modulates mitochondrial biogenesis and function and redox biology in multiple experimental models. In this chapter, we summarize RV effects on brain mitochondria to provide a better understanding of its molecular targets and mitochondrial-related parameters. Indeed, RV is a potential therapeutic agent to ameliorate mitochondrial dysfunction in different neurodegenerative disorders.
Article
Herbs, food and dietary supplements (HFDS), can interact significantly with anticancer drug treatments via cytochrome p450 isoforms (CYP) CYP3A4, CYP2D6, CYP1A2, and CYP2C8. The objective of this review was to assess the influence of HFDS compounds on these cytochromes. Interactions with CYP activities were searched for 189 herbs and food products, 72 dietary supplements in Web of Knowledge® databases. Analyses were made from 140 of 3,125 clinical trials and 236 of 3,374 in vitro, animal model studies or case reports. 18 trials were found to report direct interactions between 9 HFDS with 8 anticancer drugs. 21 HFDS were found to interact with CYP3A4, a major metabolic pathway for many anticancer drugs. All 261 HFDS were classified for their interaction with the main cytochromes P450 involved in the metabolism of anticancer drugs. We provided an easy-to-use colour-coded table to easily match potential interactions between 261 HFDS and 117 anticancer drugs.
Article
Mycological contamination of food products is a common problem in the food industry, associated with implications for consumer health. Red wine is regarded as an alcoholic beverage with health benefits, notably for the circulatory system. However, in spite of its health-promoting properties, it can also be a source of toxic substances. Wine is a documented source of ochratoxin A, which is one of the ubiquitous, highly toxic secondary metabolites produced by filamentous fungi. It is the only mycotoxin for which a regulatory maximum level in wine has been established. There are no legal regulations on the content of other mycotoxins in wine, as a product with an increased risk of mycological contamination, and so their levels are not monitored. The aim of this study was to determine the concentrations of ochratoxin A (OTA), deoxynivalenol (DON) as well as T-2 and HT-2 toxins in dry red wines. The study included 19 wines originating from Spain, France and Poland, from both conventional and organic viticulture. Mycotoxin levels were determined using immunoenzymatic assays (ELISA). The pH values were determined by potentiometric method. In all of the wines included in the study, mycotoxin levels exceeded the applicable limits. The levels of OTA and DON contamination were associated with the country of origin, and ochratoxin A was additionally linked to the farming method and certification status. The content of T-2 and HT-2 toxins was the only parameter to be negatively correlated with pH. In conclusion, wine may provide a source of many mycotoxins, not only OTA but also DON T-2 and HT-2 toxins, which was shown for the first time, and it appears further research is required to establish reference values for various mycotoxins in a wider range of foodstuffs, including wine.
Article
Chronic hyperglycemia, the diagnostic biomarker of Type 2 Diabetes Mellitus (T2DM), is a condition that fosters oxidative stress and proinflammatory signals, both involved in the promotion of cellular senescence. Senescent cells acquire a proinflammatory secretory phenotype, called SASP, exacerbating and perpetuating the detrimental effects of hyperglycemia. Bioactive compounds can exert antioxidant and anti-inflammatory properties. However, the synergistic anti-inflammatory and antioxidant effects of the most extensively investigated natural compounds have not been confirmed yet in senescent cells and in hyperglycemic conditions. Here, we exposed young and replicative senescent HUVEC (yHUVEC and sHUVEC) to a high-glucose (HG) condition (45 mM) and treated them with Polydatin (POL), Curcumin (CUR) and Quercetin (QRC), alone or in combination (MIX), to mirror the anti-inflammatory component OxiDefTM contained in the novel nutraceutical GlicefenTM (Mivell, Italy). In both yHUVEC and sHUVEC, the MIX significantly decreased the expression levels of inflammatory markers, such as MCP-1, IL-1β and IL-8, and ROS production. Importantly, in sHUVEC, a synergistic effect of the MIX was observed, suggesting its senomorphic activity. Moreover, the MIX was able to reduce the expression level of RAGE, a receptor involved in the activation of proinflammatory signaling. Overall, our data suggest that the consumption of nutraceuticals containing different natural compounds could be an adjuvant supplement to counteract proinflammatory and pro-oxidative signals induced by both hyperglycemic and senescence conditions.
Article
Purpose Resveratrol has shown promising anti-inflammatory effects in in vitro and animal studies. We aimed to investigate this effect on arterial inflammation in vivo. Methods This was an additional analysis of a double-blind randomized crossover trial which included eight male subjects with decreased insulin sensitivity who underwent an 18F-fluoroxyglucose (18F-FDG) PET/CT after 34 days of placebo and resveratrol treatment (150 mg/day). 18F-FDG uptake was analyzed in the carotid arteries and the aorta, adipose tissue regions, spleen, and bone marrow as measures for arterial and systemic inflammation. Maximum target-to-background ratios (TBRmax) were compared between resveratrol and placebo treatment with the non-parametric Wilcoxon signed-rank test. Median values are shown with their interquartile range. Results Arterial 18F-FDG uptake was non-significantly higher after resveratrol treatment (TBRmax all vessels 1.7 (1.6–1.7)) in comparison to placebo treatment (1.5 (1.4–1.6); p=0.050). Only in visceral adipose tissue, the increase in 18F-FDG uptake after resveratrol reached statistical significance (p=0.024). Furthermore, CRP-levels were not significantly affected by resveratrol treatment (p=0.091). Conclusions Resveratrol failed to attenuate arterial or systemic inflammation as measured with 18F-FDG PET in subjects at risk of developing type 2 diabetes. However, validation of these findings in larger human studies is needed.
Chapter
Polyphenols are secondary metabolites and are generally involved in defense against ultraviolet radiation, oxidative stress, or aggression by pathogens in the plant. However, there is now much interest in dietary plant polyphenols’ potential human health benefits as an antioxidant. Epidemiological studies indicate that long-term consumption of dietary polyphenols confers protection against the development of cancers, metabolic syndrome, cardiovascular diseases, diabetes, osteoporosis, and neurodegenerative diseases. The chapter describes the role of plant polyphenols as antioxidant and antioxidant in relevance to human health.
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Noncommunicable chronic diseases have been on the rise for decades. Almost 10% of the world adult population lives with type 2 diabetes mellitus (T2DM)—a leading cause of severe complications associated with disability and premature mortality. Worldwide, nearly 500 million adults are living with T2DM and 4.2 million deaths were caused directly by the disease. Dietary quality is a major component influencing the development of T2DM, due to diet-related inflammatory processes, linked to metabolically unhealthy obesity (MUO) and metabolic syndrome (MetS). In addition to systemic and tissue-specific low-grade chronic inflammation, characterized by mediators such as various cytokines, T2DM is characterized by a disturbed homeostasis of oxidative stress, as well as a dysregulated glucose and lipid metabolism. Poor inflammatory and antioxidant status have been related to an enhanced risk of developing MUO, MetS, and T2DM. However, diet also is an important source of antioxidants, which are antiinflammatory and may reduce disease risk and improve symptomology. This includes dietary patterns rich in fruits/vegetables, which are good sources of fiber, vitamins, minerals, and phytochemicals such as polyphenols, and low in animal products, ultraprocessed foods, sugar, saturated fats, total calories, and salt. Mechanistic studies have highlighted that antiinflammatory and antioxidant diets might positively influence several cellular processes. These include direct effects on the homeostasis of reactive oxygen species (ROS) such as quenching effects by antioxidants, but also the interaction of dietary constituents with transcription factors, especially with nuclear factor kappa-B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf-2), important for regulating inflammation and oxidative stress, respectively. In this chapter, we evaluate the association between dietary patterns and T2DM, as well as the role played by MUO and oxidative stress in influencing inflammation and increasing the risk of MetS and, eventually, T2DM.
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Background Haloperidol is a commonly used antipsychotic drug and may increase neuronal oxidative stress associated with the side effects, including tardive dyskinesia and neurite withdraw. Autophagy plays a protective role in response to the accumulated reactive oxygen species (ROS) induced mitochondria damage. Resveratrol is an antioxidant compound having neuroprotective effects; however, it is unknown if resveratrol may stimulate autophagy and decrease mitochondria damage induced by haloperidol. Hypothesis We hypothesis that resveratrol stimulates the autophagic process and protects mitochondria lesion induced by haloperidol. Methods MitoSOX™ Red Mitochondrial Superoxide Indicator and MitoTracker™ Green FM staining were used to measure the amount of the mitochondria ROS production and mitochondria mass in human SH-SY5Y cells treated with haloperidol and/or resveratrol. Autophagic related dyes and Western blot were applied to study the autophagic process and related protein expression. Besides, tandem monomeric mRFP-GFP-LC3 was used to investigate the fusion of autophagosome and lysosome. Transmission electron microscopy was used to investigate the mitochondrial and autophagic ultrastructures with or without haloperidol and resveratrol treatment. Results Haloperidol administration significantly increased mitochondria ROS and mitochondrial mass, indicating the increase of mitochondria dysfunction. Although haloperidol increased the autophagosomes and lysosome formation, the autophagosome-lysosome fusion and degradation were impaired. This was because we found an increased p62 after haloperidol treatment, an indication of autophagy incompletion. Importantly, resveratrol promoted the degradation of p62, upregulated the formation of autophagolysosome, and reversed haloperidol-induced mitochondria damage. Conclusion These results collectively suggest that resveratrol may be introduced as a protective compound against haloperidol-induced mitochondria impairment and aberrant autophagy.
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Phytochemicals show many desirable functions such as anti-oxidant, anti-microbial, anti-inflammatory, anti-carcinogenic, anti-aging, etc. activities. These biological functions can only be seen when the compounds are delivered at sufficient concentration. However, the bioavailability of phytonutrients suffers from their limited absorption, transformation, and rapid clearance from the circulation. In this review, we survey recent studies on the use of bile salts in lipid self-assembled systems to enhance the bioavailability of phytochemicals and consequently, their biological activity. The effect of bile salts on lipid self-assembled systems in terms of morphology, encapsulation efficiency, stability, bioavailability, and biological activities are discussed.
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Multiple myeloma (MM) is the second most common hematological cancer and causes significant mortality and morbidity. Knowledge regarding modifiable risk factors for MM remains limited. This analysis of an Australian population-based case–control family study investigates whether smoking or alcohol consumption is associated with risk of MM and related diseases. Incident cases (n = 789) of MM were recruited via cancer registries in Victoria and New South Wales . Controls (n = 1,113) were either family members of cases (n = 696) or controls recruited for a similarly designed study of renal cancers (n = 417). Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional multivariable logistic regression. Heavy intake (>20 g ethanol/day) of alcohol had a lower risk of MM compared with nondrinkers (OR = 0.68, 95% CI: 0.50–0.93), and there was an inverse dose–response relationship for average daily alcohol intake (OR per 10 g ethanol per day = 0.92, 95% CI: 0.86–0.99); there was no evidence of an interaction with sex. There was no evidence of an association with MM risk for smoking-related exposures (p > 0.18). The associations between smoking and alcohol with MM are similar to those with non-Hodgkin lymphoma. Further research into potential underlying mechanisms is warranted.
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Lingonberries contain high contents of bioactive compounds such as chlorogenic acids and anthocyanins. In addition to radical scavenging and antioxidant activities, these compounds can protect cells from DNA damage. For this reason, lingonberries might be well suited for nutraceuticals or natural biomedicines. To assess these applications, the present study characterized and identified the most effective extract, only consisting of anthocyanins, copigments or a mixture of both, obtained from a lingonberry juice concentrate. An extract was generated by using a XAD-7 column followed by fractionation into anthocyanins and copigments using adsorptive membrane chromatography. After identification of main polyphenols by HPLC–photodiode array–electrospray ionization–tandem mass spectrometry, free radical scavenging activity was analyzed by electron spin resonance spectroscopy using 2,2-diphenyl-1-picrylhydrazyl and galvinoxyl radicals. Furthermore, cyclic voltammetry analyses and the Trolox equivalent antioxidant capacity (TEAC) assay were applied. Finally, the reactive oxygen species (ROS) reducing effects of the lingonberry extract and its fractions were evaluated in HepG2 cells. While the combination of anthocyanins and copigments possessed the highest antioxidant activities, all samples (XAD-7 extract, anthocyanin and copigment fraction) protected cells from oxidative stress. Thus, synergistic effects between phenolic compounds may be responsible for the high antioxidant potential of lingonberries, enabling their use as nutraceuticals.
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In this study, the possibility of improving the bioavailability of two potent synergistic nutraceuticals, curcumin and resveratrol, using core-shell nanoparticles and its delivery through 3D printed gelatin hydrogel in a customized structure was examined. The co-axial electrospraying technique was adopted for core-shell nanoparticles formation co-encapsulating both the bioactives in zein core protected by polyethylene glycol (PEG) or ethyl cellulose (EC) as a shell. Biopolymer composition and electrospraying conditions were optimized for core-shell nanoparticle formation. Zein-PEG nanoparticles (∼300 nm) provided 68% and 83% and zein-EC nanoparticles (∼344 nm) provided 54% and 71% efficiency for curcumin and resveratrol encapsulation, respectively. Improved antioxidant activity and transition of both bioactives to amorphous form in the obtained nanoparticles were confirmed. The bioaccessibility of both bioactives was significantly improved in zein-PEG core-shell nanoparticles followed by zein-EC core-shell and simple zein nanoparticles, compared to native bioactives. The maximum bioaccessibility of 79% for curcumin and 82% for resveratrol was observed in zein-PEG core-shell nanoparticles, which is 3.6-fold and 1.7-fold higher than its native form. These nanoparticles also supported intestinal permeability enhancement by 3.5-fold and 2.2-fold for encapsulated curcumin and resveratrol, compared to its native form. To deliver these nanoparticles in consumer-preferred customized structures, 3D printing conditions were optimized to fabricate nanoparticle incorporated gelatin hydrogel 3D structures stable at room temperature. Comparatively, zein-PEG core-shell nanoparticles maintained their structural stability and uniform distribution in the hydrogel matrix for the effective protection of encapsulated bioactives. This 3D printed hydrogel model food loaded with nanoparticles will be a potent nutraceutical oral delivery system with the benefits of shape customization.
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Resveratrol is a polyphenol belonging to the class stilbenes. The active and stable form of resveratrol is trans-resveratrol. This polyphenol is bestowed with numerous biological properties. Aflatoxin B1 is a hepato-carcinogen and mutagen that is produced by Aspergillus species. In this study, the interaction of trans-resveratrol with HSA followed by competitive dislodging of AFB1 from HSA by trans-resveratrol has been investigated using spectroscopic studies. The UV-absorption studies revealed ground state complex formation between HSA and trans-resveratrol. Trans-resveratrol binds strongly to HSA with the binding constant of ~ 107 M−1 to a single binding site (n = 1.58), at 298.15 K. The Stern–Volmer quenching constant was calculated as 7.83 × 104 M−1 at 298.15 K, suggesting strong fluorescence quenching ability of trans-resveratrol. Site markers displacement assay projected subdomain IIA as the binding site of trans-resveratrol to HSA. The molecular docking approach envisages the amino acid residues involved in the formation of the binding pocket. As confirmed from the site marker displacement assays, both trans-resveratrol and AFB1 binds to HSA in the same binding site, subdomain IIA. The study explores the ability of trans-resveratrol to displace AFB1 from the HSA-AFB1 complex, thereby affecting the toxicokinetic behavior of AFB1 associated with AFB1 exposure.
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Critical limb ischemia (CLI) is a severe form of peripheral artery diseases (PAD) and seriously endangers the health of people. Therapeutic angiogenesis represents an important treatment strategy for CLI; various methods have been applied to enhance collateral circulation. However, the current development drug therapy to promote angiogenesis is limited. Resveratrol (RSV), a polyphenol compound extracted from plants, has various properties such as anti-oxidative, anti-inflammatory and anti-cancer effects. Whether RSV exerts protective effects on CLI remains elusive. In the current study, we demonstrated that oral intake of RSV significantly improved hind limb ischemia in mice, and increased the expression of phosphorylated Forkhead box class-O1 (FoxO1). RSV treatment in human umbilical vein endothelial cells (HUVECs) could increase the phosphorylation of FoxO1 and its cytoplasmic re-localization to promote angiogenesis. Then we manipulated FoxO1 in HUVECs to further verify that the effect of RSV on angiogenesis is in a FoxO1-dependent manner. Furthermore, we performed metabolomics to screen the metabolic pathways altered upon RSV intervention. We found that the pathways of pyrimidine metabolism, purine metabolism, as well as alanine, aspartate and glutamate metabolism, were highly correlated with the beneficial effects of RSV on the ischemic muscle. This study provides a novel direction for the medical therapy to CLI.
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Transthyretin (TTR) is an amyloidogenic protein, the amyloidogenic potential of which is enhanced by a number of specific point mutations. The ability to inhibit TTR fibrillogenesis is known for several classes of compounds, including natural polyphenols, which protect the native state of TTR by specifically interacting with its thyroxine binding sites. Comparative analyses of the interaction and of the ability to protect the TTR native state for polyphenols, both stilbenoids and flavonoids, and some of their main metabolites have been carried out. A main finding of this investigation was the highly preferential binding of resveratrol and thyroxine, both characterized by negative binding cooperativity, to distinct sites in TTR, consistent with the data of x-ray analysis of TTR in complex with both ligands. Although revealing the ability of the two thyroxine binding sites of TTR to discriminate between different ligands, this feature has allowed us to evaluate the interactions of polyphenols with both resveratrol and thyroxine preferential binding sites, by using resveratrol and radiolabeled T4 as probes. Among flavonoids, genistein and apigenin were able to effectively displace resveratrol from its preferential binding site, whereas genistein also showed the ability to interact, albeit weakly, with the preferential thyroxine binding site. Several glucuronidated polyphenol metabolites did not exhibit significant competition for resveratrol and thyroxine preferential binding sites and lacked the ability to stabilize TTR. However, resveratrol-3-O-sulfate was able to significantly protect the protein native state. A rationale for the in vitro properties found for polyphenol metabolites was provided by x-ray analysis of their complexes with TTR.
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Background: Myocardial fibrosis is an essential hallmark of diabetic cardiomyopathy (DCM) contributing to cardiac dysfunctions. Resveratrol, an antioxidant, exerts its anti-fibrotic effect via inhibition of oxidative stress, while the underlying molecular mechanism remains largely elusive. Periostin, a fibrogenesis matricellular protein, has been shown to be associated with oxidative stress. In the present study, we investigated the role of periostin in anti-fibrotic effect of resveratrol in streptozocin (STZ)-induced diabetic heart and the underlying mechanisms. Methods: Diabetic mice were induced by STZ injection. After treatment with resveratrol (5 or 25 mg/kg/day i.g) or Saline containing 0.5 % carboxymethyl cellulose (CMC) for 2 months, the hearts were detected for oxidative stress and cardiac fibrosis using western blot, Masson's trichrome staining and Dihydroethidium (DHE) staining. In in vitro experiments, proliferation and differentiation of fibroblasts under different conditions were investigated through western blot, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay and immunofluorescence staining. Results: Administration of resveratrol significantly mitigated oxidative level, interstitial fibrosis and expressions of related proteins in STZ-induced diabetic hearts. In in vitro experiments, resveratrol exhibited anti-proliferative effect on primary mouse cardiac fibroblasts via inhibiting reactive oxygen species (ROS)/extracellular regulated kinase (ERK) pathway and ameliorated myofibroblast differentiation via suppressing ROS/ERK/ transforming growth factor β (TGF-β)/periostin pathway. Conclusion: Increased ROS production, activation of ERK/TGF-β/periostin pathway and myocardial fibrosis are important events in DCM. Alleviated ROS genesis by resveratrol prevents myocardial fibrosis by regulating periostin related signaling pathway. Thus, inhibition of ROS/periostin may represent a novel approach for resveratrol to reverse fibrosis in DCM.
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Background: Silence of the tumor suppressor miR-34c is implicated in the development of colorectal cancer (CRC). For the past few years, Resveratrol (Res) has been introduced to oncotherapies alone or with traditional chemotherapeutic drugs. However, the study of molecular mechanism involved in the anti-CRC effect of Res is still ongoing. Methods: The anti-CRC effect of Res alone or with Oxaliplatin (Oxa) was determined by cell viability assay, soft agar colony formation assay, flow cytometry and real-time cellular analyzer in HT-29 (p53 (+) ) and HCT-116 (p53 (-) ) CRC cell lines. Expressions of miR-34c and its targets were detected by qPCR and/or western blot. To evaluate the role of miR-34c in anti-CRC effect by Res alone or with Oxa, miR-34c was up or down-regulated by lentiviral mediation or specific inhibitor, respectively. To investigate how miR-34c was increased by Res, the methylation status of miR-34c promoter was detected by MSP. The tumor bearing mouse model was established by subcutaneous injection of HCT-116 cells to assess anti-CRC effect of Res alone or with Oxa in vivo. IL-6 and TNF-α in xenografts were detected by ELISA. Results: Res inhibited cell viability, proliferation, migration and invasion as well as promoted apoptosis both in HT-29 and HCT-116 CRC cells. The anti-CRC effect of Res was partially but specifically through up-regulating miR-34c which further knocked down its target KITLG; and the effect was enhanced in the presence of p53 probably through inactivating PI3K/Akt pathway. Besides, Res sensitized CRC cells to Oxa in a miR-34c dependent manner. The xenograft experiments showed that exposure to Res or Oxa suppressed tumor growth; and the efficacy was evidently augmented by the co-treatment of Res and Oxa. Likewise, miR-34c level was elevated in xenografts of Res-treated mice while the KITLG was decreased. Finally, Res clearly reduced IL-6 in xenografts. Conclusion: Res suppressed CRC by specifically activating miR-34c-KITLG in vitro and in vivo; and the effect was strengthened in the presence of p53. Besides, Res exerted a synergistic effect with Oxa in a miR-34c dependent manner. We also suggested that Res-increased miR-34c could interfere IL-6-triggered CRC progression.
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Proliferative vitreoretinopathy (PVR) is a serious complication of retinal detachment and ocular trauma, and its recurrence may lead to irreversible vision loss. Epithelial to mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a critical step in the pathogenesis of PVR, which is characterized by fibrotic membrane formation and traction retinal detachment. In this study, we investigated the potential impact of resveratrol (RESV) on EMT and the fibrotic process in cultured RPE cells and further examined the preventive effect of RESV on PVR development using a rabbit model of PVR. We found that RESV induces mesenchymal to epithelial transition (MET) and inhibits transforming growth factor-β2(TGF-β2)-induced EMT of RPE cells by deacetylating SMAD4. The effect of RESV on MET was dependent on sirtuin1 activation. RESV suppressed proliferation, migration and fibronectin synthesis induced by platelet-derived growth factor-BB or TGF-β2. In vivo, RESV inhibited the progression of experimental PVR in rabbit eyes. Histological findings showed that RESV reduced fibrotic membrane formation and decreased α-SMA expression in the epiretinal membranes. These results suggest the potential use of RESV as a therapeutic agent to prevent the development of PVR by targeting EMT of RPE.
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Our current understanding on the molecular mechanisms by which sustained compression induces skeletal muscle injury is very limited. This study aimed to test the hypothesis that activation of SIRT1 by the natural antioxidant resveratrol could deactivate apoptotic and catabolic signaling in skeletal muscle exposed to moderate compression. Two cycles of 6-h constant pressure at 100 mmHg was applied to the tibialis region of right, but not left hindlimbs of Sprague Dawley rats pre-treated with DMSO (vehicle control) or resveratrol with/without sirtinol. Skeletal muscle tissues lying underneath and spatially corresponding to the compressed sites were collected for analyses. Resveratrol prevented the compression-induced manifestations of pathohistological damages including elevations of the number of interstitial nuclei and area of interstitial space and ameliorated oxidative damages measured as 4-hydroxy-2-nonenal (4HNE) and nitrotyrosine in skeletal muscle. In parallel, resveratrol augmented the expression level and activity of SIRT1 and phosphorylation levels of Foxo3a and Akt while suppressed the increases in protein abundances of p53, Bax, MAFbx, and ubiquitin, enzymatic activities of caspase 3 and 20S proteasome, and apoptotic DNA fragmentation in the compressed muscle. These favorable myoprotective effects of resveratrol were diminished upon pharmacological blockade of SIRT1 by using sirtinol. These novel data support the hypothesis that the anti-apoptotic and anti-catabolic effects of resveratrol on compression injury in skeletal muscle required the action of SIRT1.
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Resveratrol (3, 5, 4′-trihydroxy-trans-stilbene), a plant polyphenol, has important drug-like properties, but its pharmacological exploitation in vivo is hindered by its rapid transformation via phase II conjugative metabolism. One approach to bypass this problem relies on prodrugs. We report here the synthesis, characterization, stability and in vivo pharmacokinetic behaviour of prodrugs of resveratrol in which the OH groups are engaged in an N-monosubstituted carbamate ester (-OC(O) NHR) linkage with a natural amino acid (Leu, Ile, Phe, Thr) to prevent conjugation and modulate the physicochemical properties of the molecule. We also report a convenient, high-yield protocol to obtain derivatives of this type. The new carbamate ester derivatives are stable at pH 1, while they undergo slow hydrolysis at physiological pH and hydrolyse with kinetics suitable for use in prodrugs in whole blood. After administration to rats by oral gavage the isoleucine-containing prodrug was significantly absorbed, and was present in the bloodstream as non-metabolized unaltered or partially deprotected species, demonstrating effective shielding from first-pass metabolism. We conclude that prodrugs based on the N-monosubstituted carbamate ester bond have the appropriate stability profile for the systemic delivery of phenolic compounds.
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Despite advances in neonatal care, hypoxic-ischemic brain injury is still a serious clinical problem, which is responsible for many cases of perinatal mortality, cerebral palsy, motor impairment and cognitive deficits. Resveratrol, a natural polyphenol with important anti-oxidant and anti-inflammatory properties, is present in grapevines, peanuts and pomegranates. The aim of the present work was to evaluate the possible neuroprotective effect of resveratrol when administered before or immediately after a hypoxic-ischemic brain event in neonatal rats by analyzing brain damage, the mitochondrial status and long-term cognitive impairment. Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response. Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood. We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species. Curiously, none of these protective features was observed when resveratrol was administered immediately after hypoxia-ischemia.
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Background: Non-alcoholic steatohepatitis (NASH) is one of the leading causes of chronic liver disease that can progress to liver fibrosis, cirrhosis and eventually hepatocellular carcinoma. Resveratrol, a naturally occurring phytoalexin, is believed to have therapeutic effects on hepatic steatosis. However, the effect of resveratrol on NASH and the underlying mechanism is not fully illustrated. In the present study, we aimed to exam the effect of resveratrol on methionine/choline-deficient (MCD) diet or medium-induced hepatic steatosis, oxidation and inflammation, and to explore the possible mechanism. Methods: C57BL/6 mice and AML12 cells were treated with MCD alone or in combination with different concentrations of resveratrol (100 mg/kg/day or 250 mg/kg/day for mice and 25 μmol/L, 50 μmol/L, or 100 μmol/L for cells). Levels of aminotransferases (ALT), interleukin 1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) were measured, concentrations of triglyceride (TG) and thiobarbituric acid reactive substances (TBARs) were determined, and expressions of proteins involved in autophagy were analyzed. Results: The results indicate that MCD diet or medium induced NASH in mouse and AML12 cell, which was confirmed by the elevated levels of TG, TNF-α, IL-1β, IL-6, ALT and TBARS in mice serum or cell culture medium. Resveratrol administration slowed down NASH progression, decreased the levels of ALT, TG, TBARS, IL-1β, IL-6, downregulated mRNA expressions of TNF-α, IL-1β, IL-6, and regulated the expressions of proteins involved in autophagy, both in vitro and in vivo. However, an autophagical inhibitor significantly impaired the protective role of resveratrol on liver injury and inflammation. Conclusions: Resveratrol can attenuate hepatic steatosis and inflammation in MCD-induced NASH by regulating autophagy. Thus, resveratrol may be a promising agent for inhibiting lipid accumulation and inflammatory processes associated with NASH.
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Diabetes adversely affects reproductive functions in humans and animals. The present study investigated the effects of Resveratrol on diabetes-induced alterations in oxidative stress, c-Jun N-terminal kinase (JNK) signaling and apoptosis in the testis. Adult male Wistar rats (13–15 weeks; n = 6/group) were segregated into 1) normal control, 2) Resveratrol-treated (5 mg/kg; ip; given during last 3 weeks), 3) Streptozotocin-induced diabetic and, 4) Resveratrol-treated diabetic groups, and euthanized on day 42 after the confirmation of diabetes. Resveratrol did not normalize blood glucose levels in diabetic rats. Resveratrol supplementation recovered diabetes-induced decreases in reproductive organ weights, sperm count and motility, intra-testicular levels of superoxide dismut-ase, catalase, and glutathione peroxidase and an increase in 4-hydroxynonenal activities (P b 0.05). Resveratrol also recovered diabetes-induced increases in JNK signaling pathway proteins, namely, ASK1 (apoptosis signal-regulating kinase 1), JNKs (46 and 54 kDa isoforms) and p-JNK to normal control levels (P b 0.05). Interestingly, the expression of a downstream target of ASK1, MKK4 (mitogen-activated protein kinase kinase 4) and its phos-phorylated form (p-MKK4) did not change in experimental groups. Resveratrol inhibited diabetes-induced increases in AP-1 (activator protein-1) components, c-Jun and ATF2 (activating transcription factor 2), but not their phosphorylated forms, to normal control levels (P b 0.05). Further, Resveratrol inhibited diabetes-induced increase in cleaved-caspase-3 to normal control levels. In conclusion, Resveratrol alleviates diabetes-induced apoptosis in testis by modulating oxidative stress, JNK signaling pathway and caspase-3 activities, but not by inhibiting hyperglycemia, in rats. These results suggest that Resveratrol supplementation may be a useful strategy to treat diabetes-induced testicular dysfunction.
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Background: Resveratrol may play a protective role against the frailty syndrome (FS) because of its antioxidant and anti-inflammatory properties. Objective: We prospectively evaluated the association between habitual dietary resveratrol exposure and the development of FS after 3-, 6-, and 9-y follow-up periods in a community-dwelling older population. Design: We conducted a longitudinal analysis with the use of data from 769 participants aged ≥65 y from the Invecchiare in Chianti (Aging in Chianti) study. Total dietary resveratrol (TDR) intake was estimated at baseline with the use of a validated food-frequency questionnaire, which was developed to assess participants' usual food intakes over the previous year, and an ad hoc resveratrol database. Total urinary resveratrol (TUR) was analyzed with the use of liquid chromatography-tandem mass spectrometry with a previous solid-phase extraction at baseline. The combination of both measures [total dietary resveratrol plus total urinary resveratrol (TDR+TUR)] was computed with the use of the Howe's method. FS was assessed at baseline and at 3-, 6-, and 9-y of follow-up and was defined as the presence of ≥3 of the following 5 criteria: shrinking, exhaustion, sedentariness, slowness, and weakness. Results: TDR+TUR concentrations were inversely associated with FS risk over 3-y of follow-up (OR for comparison of extreme tertiles: 0.11; 95% CI: 0.03, 0.45; P-trend = 0.002) but not after 6- and 9-y of follow-up in multinomial logistic regression models adjusted for baseline frailty status and potential confounders. These results did not differ when analyses were further adjusted for inflammatory markers. Conclusion: Higher habitual dietary resveratrol exposure was associated with lower risk of older community dwellers developing FS during the first 3 y of follow-up but not after longer follow-up periods.
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Physical inactivity reduces, and exercise training increases, mitochondrial capacity. In rodents, exercise training effects can be augmented by large doses of resveratrol supplementation but whether this can occur in humans with a smaller dose is unclear. This study sought to determine the effects of resveratrol supplementation in combination with exercise training on skeletal muscle mitochondrial capacity. Sixteen healthy young adults were randomly assigned in a double-blind fashion to consume either placebo or 500 mg of resveratrol plus 10 mg of piperine, a bioenhancer to increase bioavailibilty and bioefficacy of resveratrol. Participants ingested the pills daily for 4 weeks and completed 3 sessions per week of submaximal endurance training of the wrist flexor muscles of the nondominant arm. The contralateral arm served as an untrained control. Skeletal muscle mitochondrial capacity was measured using near-infrared spectroscopy. Changes in mitochondrial capacity from baseline to post-testing indicated significant differences between the resveratrol+piperine-trained arm and the placebo-trained arm (p = 0.02), with the resveratrol+piperine group increasing about 40% from baseline (Δk = 0.58), while the placebo group increased about 10% from baseline (Δk = 0.13). Neither the placebo group nor the resveratrol+piperine group exhibited changes in mitochondrial capacity in the untrained arm. In conclusion, low-intensity exercise training can increase forearm skeletal muscle mitochondrial capacity when combined with resveratrol and piperine supplementation.
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Background: Nutrition is believed to be a primary contributor in regulating gene expression by affecting epigenetic pathways such as DNA methylation and histone modification. Resveratrol and pterostilbene are phytoalexins produced by plants as part of their defense system. These two bioactive compounds when used alone have been shown to alter genetic and epigenetic profiles of tumor cells, but the concentrations employed in various studies often far exceed physiologically achievable doses. Triple-negative breast cancer (TNBC) is an often fatal condition that may be prevented or treated through novel dietary-based approaches. Methods: HCC1806 and MDA-MB-157 breast cancer cells were used as TNBC cell lines in this study. MCF10A cells were used as control breast epithelial cells to determine the safety of this dietary regimen. CompuSyn software was used to determine the combination index (CI) for drug combinations. Results: Combinatorial resveratrol and pterostilbene administered at close to physiologically relevant doses resulted in synergistic (CI <1) growth inhibition of TNBCs. SIRT1, a type III histone deacetylase (HDAC), was down-regulated in response to this combinatorial treatment. We further explored the effects of this novel combinatorial approach on DNA damage response by monitoring γ-H2AX and telomerase expression. With combination of these two compounds there was a significant decrease in these two proteins which might further resulted in significant growth inhibition, apoptosis and cell cycle arrest in HCC1806 and MDA-MB-157 breast cancer cells, while there was no significant effect on cellular viability, colony forming potential, morphology or apoptosis in control MCF10A breast epithelial cells. SIRT1 knockdown reproduced the effects of combinatorial resveratrol and pterostilbene-induced SIRT1 down-regulation through inhibition of both telomerase activity and γ-H2AX expression in HCC1806 breast cancer cells. As a part of the repair mechanisms and role of SIRT1 in recruiting DNMTs, the effects of this combination treatment was also explored on DNA methyltransferases (DNMTs) expression. Interestingly, the compounds resulted in a significant down-regulation of DNMT enzymes with no significant effects on DNMT enzyme expression in MCF10A control cells. Conclusion: Collectively, these results provide new insights into the epigenetic mechanisms of a novel combinatorial nutrient control strategy that exhibits synergy and may contribute to future recalcitrant TNBC prevention and/or therapy.
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Reducing oxidative stress is crucial to preventing hypoxia-reoxygenation (H/R)-induced lung injury. Resveratrol has excellent antioxidant and anti-inflammatory effects, and this study investigated its role in H/R-induced type II pneumocyte dysfunction. H/R conditions increased expression of inflammatory cytokines including interleukin (IL)-1β (142.3±21.2%, P < 0.05) and IL-6 (301.9±35.1%, P < 0.01) in a type II alveolar epithelial cell line (A549) while the anti-inflammatory cytokine IL-10 (64.6±9.8%, P < 0.05) and surfactant proteins (SPs) decreased. However, resveratrol treatment effectively inhibited these effects. H/R significantly activated an inflammatory transcription factor, nuclear factor (NF)-κB, while resveratrol significantly inhibited H/R-induced NF-κB transcription activities. To the best of our knowledge, this is the first study showing resveratrol-mediated reversal of H/R-induced inflammatory responses and dysfunction of type II pneumocyte cells in vitro. The effects of resveratrol were partially mediated by promoting SP expression and inhibiting inflammation with NF-κB pathway involvement. Therefore, our study provides new insights into mechanisms underlying the action of resveratrol in type II pneumocyte dysfunction.
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Transthyretin (TTR) is an amyloidogenic protein, whose amyloidogenic potential is enhanced by a number of specific point mutations. The ability to inhibit TTR fibrillogenesis is known for several classes of compounds, including natural polyphenols, which protect the native state of TTR by specifically interacting with its thyroxine binding sites. Comparative analyses of the interaction and of the ability to protect the TTR native state for polyphenols, both stilbenoids and flavonoids, and some of their main metabolites have been carried out. A main finding of this investigation was the highly preferential binding of resveratrol and thyroxine, both characterized by negative binding cooperativity, to distinct sites in TTR, consistent with the data of X-ray analysis of TTR in complex with both ligands. While revealing the ability of the two thyroxine binding sites of TTR to discriminate between different ligands, this feature has allowed us to evaluate the interactions of polyphenols with both resveratrol and thyroxine preferential binding sites, by using resveratrol and radiolabeled T4 as probes. Among flavonoids, genistein and apigenin were able to effectively displace resveratrol from its preferential binding site, while genistein also showed the ability to interact, albeit weakly, with the preferential thyroxine binding site. Several glucuronidated polyphenol metabolites did not exhibit significant competition for resveratrol and thyroxine preferential binding sites, and lacked the ability to stabilize TTR. However, resveratrol-3-O-sulphate was able to significantly protect the protein native state. A rationale for the in vitro properties found for polyphenol metabolites was provided by X-ray analysis of their complexes with TTR.
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Resveratrol, a natural polyphenolic compound known for its antioxidative and antiinflammatory effects, exerts antiasthmatic effects, although the mechanism underlying these effects remains elusive. The phosphatase and tensin homology deleted on chromosome ten gene (PTEN) is involved in the pathogenesis of asthma, and PTEN overexpression in asthmatic mice improved asthma symptoms. To investigate whether the antiasthmatic mechanisms of resveratrol correlated with the upregulation of PTEN expression, an ovalbumin (OVA)-induced murine asthma model was used to determine the effectiveness of resveratrol treatment. PTEN mRNA and protein expression was assessed with real-time PCR and immunochemistry. To determine whether airway remodeling occurred, the inner airway wall, mucous layer, and smooth muscle areas were each determined using an image analysis system. The lung epithelial cell line 16HBE was used to study the regulation of PTEN expression levels by resveratrol in vitro. Our data demonstrated that resveratrol inhibited OVA-induced airway inflammation and airway remodeling in asthmatic mice. PTEN expression was decreased in the murine asthma model, although the expression of PTEN was restored following treatment with resveratrol. Correlation efficiency analysis showed that PTEN expression was associated with the degree of airway remodeling. Further in vitro studies demonstrated that the inhibition of SIRT1 activity by a SIRT1 inhibitor and RNA interference decreased PTEN protein expression, while resveratrol attenuated the decreases in PTEN expression induced by the SIRT1 inhibitor. These data suggest the mechanism of the antiasthmatic effects of resveratrol in an OVA-induced murine asthma model, which resulted in the upregulation of PTEN via SIRT1 activation.
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